The present invention relates to antimicrobial polymeric compositions. More particularly, the antimicrobial polymeric compositions of the present invention contain compounds having a polyacrolein sub-unit with its aldehyde group in its free, hydrated, hemi-acetal or acetal form, and having biostatic and/or biocidal properties. The invention is directed to compositions containing these polymeric compounds and the biostatic and/or biocidal uses of these compositions.
The broad-based antimicrobial properties of polymers (hereinafter called the xe2x80x9csubject polymersxe2x80x9d) having the repeating polymeric unit: 
or this unit in its hydrated, hemi-acetal or acetal form, represented by the formulae: 
wherein R is hydrogen or alkyl and n is an integer of one or more, have been demonstrated previously (Melrose et al., International Patent Publication WO 88/04671). The subject polymers described therein include poly(2-propenal, 2-propenoic acid).
It has also been noted previously (Melrose, International Patent Publication WO 96/38186) that poly(2-propenal, 2-propenoic acid) is formed when the aldehyde groups of poly(2-propenal) syn polyacrolein are partially auto-oxidised to carboxyl groups, by heating the dry polymer in air, to 100xc2x0 C. and preferably to between 80xc2x0 C. and 100xc2x0 C. It was further noted that the resulting polymer is soluble in dilute aqueous bases, for example aqueous sodium carbonate.
An earlier disclosure (Werle et al., Australian Patent Application 11686/95, now lapsed) claimed solubility of the subject polymers in polyolsxe2x80x94but not solubility in aqueous media, following heating to 75xc2x0 C. It was further claimed that subsequent to the heating to 75xc2x0 C., brief treatment with sodium hydroxide gave rise to aqueous solubility and apparently as a result, increased antimicrobial activity.
To increase the stability of compositions containing the subject polymers, Melrose and Huxham (International Patent Application PCT/AU99/00578) have formulated compositions with anionic surfactants. Additionally, this prior art revealed that in basic compositions, in contrast to acidic compositions, the subject polymers have faster antimicrobial activity, but are less stable.
It is particularly desirable that the subject polymers should not be unstable, yielding acrolein, as this monomer is very irritating to the eyes, lungs, tissues and skin.
It is one object of the present invention to provide methods of preparing compositions, these methods producing a new configuration of the subject polymers and in particular of poly(2-propenal, 2-propenoic acid), and which have enhanced antimicrobial activity.
It is a further object of the present invention to provide methods of preparing compositions, these methods producing a new configuration of the subject polymers and in particular of poly(2-propenal, 2-propenoic acid), and which better retain antimicrobial activity.
It is a still further object of the present invention to provide methods of preparing compositions, these methods producing a new configuration of the subject polymers and in particular of poly(2-propenal, 2-propenoic acid), and which contain less free acrolein.
It is a yet still further object of the present invention to provide compositions containing a new configuration of the subject polymers and in particular of poly(2-propenal, 2-propenoic acid) which are efficacious disinfectants or antiseptics.
Throughout the specification, unless the context requires otherwise, the word xe2x80x9ccomprisexe2x80x9d or variations such as xe2x80x9ccomprisesxe2x80x9d or xe2x80x9ccomprisingxe2x80x9d, will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers.
In accordance with the present invention there is provided a method for improving the antimicrobial activity of a polymer derived from acrolein monomer wherein the polymer has been oxidized in air to form an oxidised acrolein polymer comprising carboxyl groups, said method comprising:
providing a solution of the oxidized acrolein polymer comprising carboxyl groups in a mixture containing water and a hydroxylic solvent including an alcohol selected from the group consisting of polyols, polyethylene glycols and alkanols; and
heating the solution at a temperature in the range of from 40 to 150xc2x0 C. for a period sufficient to improve the antimicrobial activity of the acrolein polymer.
Still preferably, the polymers are heated in the range of 40 to 115xc2x0 C.
Still further preferably, the polymers are heated in the range of 70-90xc2x0 C.
Preferably, the polymers are heated for a period of between 1 to 1,400 hours, thereby increasing antimicrobial activity of the polymers.
Still preferably, the polymers are heated for a period of between 10 to 60 hours.
In one form of the invention the polymers are heated in the presence of one or more of polyethylene glycol, polyol or alkanol, thereby providing one or both of enhanced stability or enhanced anti microbial activity. Water is invariably present in these alcohols.
Preferably, polyethylene glycol is present during the preparation of the polymers in the amount of between 50 and 99% by weight.
Still preferably, poly ethylene glycol is present during preparation of the polymers in the amount of between 64 and 95% by weight.
In a further form of the invention, base or alkali is added to the polymers before and/or during heating, thereby enhancing the antimicrobial activity of the polymers.
Preferably, the addition of the base or alkali brings the pH of the polymers to between 7 and 9.
Still preferably, the pH is about 8. Sodium hydroxide may be the base added.
In a still further form of the invention, the release of free acrolein monomer is inhibited, thereby the polymers are less likely to present a source of tissue or dermal irritation.
Preferably, the polymer is initially heated, predominantly in the dry state, to between 80 and 100xc2x0 C.
Still preferably, the polymer is initially heated to about 85xc2x0 C.
In accordance with the present invention there is further provided an antimicrobial compound or composition prepared by one or more of the methods described hereinabove.
In accordance with the present invention there is still further provided a preservative compound or composition prepared by one or more of the methods described hereinabove.
In accordance with the present invention there is yet still further provided a disinfectant or antiseptic compound or composition prepared wholly or in part by the methods described hereinabove.
Preferably, the disinfectant or antiseptic compound or composition has a pH greater than 6, thereby enhancing antimicrobial activity.
In accordance with the present invention, there are provided methods for the preparation of a new configuration of the subject polymers including poly(2-propenal, 2-propenoic acid) and of compositions therefrom, whereby the compositions exhibit increased antimicrobial activity, and/or increased stability and/or contain less free acrolein, thus making the polymers and/or their compositions more suitable as preservatives, and/or active ingredients in disinfectants and/or, antiseptics, under acidic or basic conditions.
Since the prior art recorded some instability of poly(2-propenal, 2-propenoic acid), as evidenced by loss of antimicrobial activity of its compositions, the routine procedure in industry was then followed in our laboratories, of quantitatively determining this instability by standard xe2x80x9caccelerated ageingxe2x80x9d at elevated temperature, ie. at 40xc2x0 C. However, to our greatest surprise, the elevated temperature of xe2x80x9cageingxe2x80x9d poly(2-propenal, 2-propenoic acid) in aqueous or in aqueous-polyethylene glycol solutions at 40xc2x0 C., not only slowed the decrease in antimicrobial activityxe2x80x94but in fact, actually increased antimicrobial activity of the poly(2-propenal, 2-propenoic acid), see Example 2(a) and (b). This finding is totally contradictory and unexpected in view of the prior art which predicts that the rise in temperature should lead to xe2x80x9caccelerated ageingxe2x80x9d, ie. accelerated loss of antimicrobial activity.
Henceforth, the process of providing increased antimicrobiological activity by the formation of a new configuration of the subject polymers including poly(2-propenal, 2-propenoic acid), is referred to as xe2x80x9csuper-activationxe2x80x9d and the polymers referred to as xe2x80x9csuper-activated polymersxe2x80x9d.
Even more surprising, in view of prior art, the inventors have found super-activation in aqueous polyethylene glycol solution is promoted by basic conditions, see Example 2(c).
Also, super-activation is promoted by heat and moisture, alone, see Example 4.
Additionally, it has been found that prior, dry heating of the subject polymers between 80-65xc2x0 C. gives polymers, see Example 1, which are soluble in aqueous media and suitable for subsequent super-activation.
Super-activation is facilitated by the presence of polyethylene glycols or polyols or alkanols see Example 3, xe2x80x94we believe, since the presence of the polyethylene glycol or polyol or alkanol protects and stabilises the carbonyl groups of the polymers, possibly by formation of acetals, from alkaline degradation by the Cannizarro reaction.
An added advantage of super-activation is that it gives rise to less, contaminant acrolein which is a source of tissue and dermal irritation, see Example 6.
It is emphasised that super-activation is quite distinct and additional to any increase of antimicrobial activity which may result, merely from more polymer being available in any aqueous test-medium as the result of increased hydrophillicity of the polymer such as was demonstrated in lapsed Australian Patent Application AU-A-11686/95 (hereinafter xe2x80x9c11686/95xe2x80x9d). The inventors have repeated exactly the method described in 11686/95 and then, following, found that subsequent super-activation of the partially soluble polymer demonstratively gave rise to additional, substantial antimicrobial activity, see Example 5. It should be noted that even super-activation did not render the polymer from 11686/95 completely solublexe2x80x94in contrast to super-activation beginning with polymer firstly heated between to 80-85xc2x0 C.
The optimum time to achieve super-activation of solutions of poly(2-propenal, 2-propenoic acid) depends inversely upon the temperature, see Example 7. It will be apparent that even ageing at room temperature may be used for super-activation, especially when facilitated in the presence of hydroxylic solvent and/or base, but obviously, this may be impractical due to the longer time periods required.
The inventors have found polymers super-activated as described herein, suitable for preservatives in water-based products or processes, and as well, as active ingredients in disinfectants or antiseptics having the advantage of enhanced antimicrobial activity, see Example 8. Furthermore, the inventors found that the antimicrobial activity of such disinfectants or antiseptics was increased by increase in their pH, for example above pH 6, see again Example 8.
The invention will now be described with reference to several Examples, which should not be construed as limiting the scope thereof.
Dilute sample with 1% aqueous sodium bicarbonate to obtain the required concentration (unless specified to the contrary, 0.125% in polymer). Weight 19.9 g of diluted sample into a sterile jar and inoculate with 0.1 mL of 107-108 suspension of Ps.aeruginosa and mix. At specified time-intervals, transfer 1 mL of inoculated sample to 9 mL of letheen broth and vortex. Plate out serial 1 in 10 dilutions. Pour with tryptone soya agar. Incubate 3 days at 37xc2x0 C.